Autoimmunity and emphysema and risk of osteoporosis in smokers

吸烟者的自身免疫和肺气肿以及骨质疏松症的风险

• 批准号: 9916794
• 负责人: JESSICA BON
• 金额: $ 38.5万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9916794
• 关键词: Age; Alveolar Macrophages; Antibodies; Autoantibodies; Autoimmune Process; Autoimmune Responses; Autoimmunity; Binding; Binding Proteins; Biological Assay; Biological Markers; Bone Density; Cachexia; Cause of Death; Cells; Chronic Obstructive Airway Disease; Data; Dentin; Diagnostic radiologic examination; Disease; Disease Progression; Endoplasmic Reticulum; Enzyme-Linked Immunosorbent Assay; Female; Foundations; Fracture; Future; Goals; Heat shock proteins; High Prevalence; Human; Immune Targeting; Immune response; Immunoglobulin G; Immunohistochemistry; Immunologic Markers; Immunologics; Immunomodulators; In Vitro; Incidence; Inflammation Mediators; Inflammatory; Investigational Therapies; Link; Literature; Longitudinal cohort; Lung diseases; Measurement; Measures; Mediating; Molecular; Molecular Chaperones; Morbidity - disease rate; NF-kappa B; Natural History; Osteoclasts; Osteoporosis; Osteoporosis prevention; Participant; Pathogenesis; Pathogenicity; Pathologic; Patient Selection; Patients; Physical activity; Physiological; Population; Prevalence; Prevention strategy; Process; Production; Proteins; Pulmonary Emphysema; Reaction Time; Reverse Transcriptase Polymerase Chain Reaction; Risk; Risk Factors; Risk stratification; Roentgen Rays; Role; Scanning; Series; Smoker; Smoking Status; Stains; Steroids; Testing; United States; Variant; Woman; X-Ray Computed Tomography; airway obstruction; biological adaptation to stress; bone; bone resorbing activity; bone turnover; clinically significant; cohort; cytokine; endoplasmic reticulum stress; falls; follow-up; glucose-regulated proteins; improved; insight; male; men; mortality; novel; nuclear factors of activated T-cells; osteoporosis with pathological fracture; patient population; physical inactivity; precursor cell; public health relevance; pulmonary function; response; screening guidelines; smoking-related lung disease; targeted agent; tartrate-resistant acid phosphatase; time interval; tool; treatment strategy

 DESCRIPTION (provided by applicant): Low bone mineral density (BMD) has been linked to chronic obstructive pulmonary disease (COPD) independent of traditional osteoporosis risk factors including steroid use, cachexia, and decreased physical activity. Although the increased prevalence of osteoporosis contributes to morbidity and mortality in COPD patients, little is known regarding indications for BMD assessment or osteoporosis mechanisms in this susceptible population. The rate of BMD loss is an independent risk factor for fracture. Yet, cross-sectional dual x-ray absorptiometry (DXA) assessment of BMD provides no information about rate of BMD decline. Immunologic alterations contribute to the pathogenesis of both COPD and osteoporosis but the role of autoimmunity in COPD-related osteoporosis has not been studied. An independent association between emphysema and low BMD has been supported by the literature, but the mechanism for this association is also unknown. This project's overall goal is to study how specific autoimmune processes relate to concurrent emphysema progression and accelerated BMD decline in male and female smokers with lung disease. This goal will be accomplished through extension to six years of an already established longitudinal cohort with pre- existing baseline and two-year assessments of BMD, radiographic emphysema, pulmonary function, and autoimmune biomarker levels. The association of an autoimmune biomarker, anti-glucose regulated protein 78 (GRP78) IgG, with emphysema progression, measured by quantitative CT scan, and BMD loss, measured by serial DXA, over the six-year time interval will be studied in smokers with emphysema or airflow obstruction. A series of in vitro osteoclast studies will be performed to assess the effect of autoantibodies to GRP78, an endoplasmic reticulum (ER) chaperone protein intimately involved in the ER stress response, on osteoclast formation, proliferation, and activity. The findings from this project will identify criteria for smokers at risk of accelerated BMD loss in whom early and serial measurements of BMD may be warranted, provide insight into pathogenic mechanisms linking emphysema and osteoporosis, and provide novel targets for osteoporosis prevention and treatment strategies in patients with COPD.